2020-08-28 tc1590_M1SD INCLUDEINTERPOLATION controls not working as expected or consistently.

[TomTensfeldt]

No issues noted with extrapolation. However there is a bug with Inclusion/Exclusion of interpolation. For 44 out of the 48 profiles in the dataset, behavior is as expected, but there is a problem with some AUC results for 4 profiles where interpolation is required.

Please review attached document for details. tc1590_Deviation_Summary_28Aug2020.docx

[jhhughes256]

This comment provides an example of the behaviour of the CE with commit cca452d for reference.

Include interpolation and extrapolation

No issues with commit cca452d

knitr::kable(head(oldData[,c(1, grep("^AUC\\d+_\\d+$", names(oldData)), grep("^CONCTIME\\d+$", names(oldData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	19.037484	62.309949	91.60590	98.11387	63.098301	65.724934	36.732628	7.3711403	6.4956227	13.778151	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	3.891138	15.775430	22.48847	24.74776	15.219666	16.092465	8.411666	2.3810272	2.0219357	4.556427	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	4.864913	9.248423	15.22506	15.17522	6.130309	6.720872	2.296925	0.0535589	0.0566612	3.893736	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	5.104697	16.115864	23.68840	23.82780	12.812288	13.719644	6.291580	0.3397483	0.3787301	5.177265	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	16.627023	27.186570	47.45846	47.69749	19.245042	21.009201	7.445251	0.1791732	0.1901194	11.044250	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	1815.233049	1140.509935	3149.77397	3189.45272	832.210865	907.337515	361.931940	44.3411132	37.0634435	546.902894	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

Include extrapolation, exclude interpolation

Issues with commit cca452d. 4 profiles have values reported for AUC0_64, 60_100 and 60_124 when they should be missing as they include interpolated timepoints 60 and 64.

knitr::kable(head(oldData[,c(1, grep("^AUC\\d+_\\d+$", names(oldData)), grep("^CONCTIME\\d+$", names(oldData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	NA	62.309949	NA	98.11387	63.098301	NA	36.732628	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	NA	15.775430	NA	24.74776	15.219666	NA	8.411666	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	NA	9.248423	15.22506	15.17522	6.130309	NA	2.296925	0.0535589	0.0566612	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	NA	16.115864	23.68840	23.82780	12.812288	NA	6.291580	0.3397483	0.3787301	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	NA	27.186570	47.45846	47.69749	19.245042	NA	7.445251	0.1791732	0.1901194	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	NA	1140.509935	NA	3189.45272	832.210865	NA	361.931940	NA	NA	NA	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

Exclude interpolation and extrapolation

No issues with commit cca452d

knitr::kable(head(oldData[,c(1, grep("^AUC\\d+_\\d+$", names(oldData)), grep("^CONCTIME\\d+$", names(oldData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	NA	62.309949	NA	NA	NA	NA	NA	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	NA	15.775430	NA	NA	NA	NA	NA	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	NA	9.248423	NA	NA	NA	NA	NA	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	NA	16.115864	NA	NA	NA	NA	NA	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	NA	27.186570	NA	NA	NA	NA	NA	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	NA	1140.509935	NA	NA	NA	NA	361.9319	NA	NA	NA	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

Include interpolation, exclude extrapolation

Issues with commit cca452d. 4 profiles have values not reported reported for AUC0_64 when they should report a value as 0 and 64 are not extrapolated values.

knitr::kable(head(oldData[,c(1, grep("^AUC\\d+_\\d+$", names(oldData)), grep("^CONCTIME\\d+$", names(oldData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	19.037484	62.309949	91.60590	NA	NA	NA	NA	NA	NA	13.778151	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	3.891138	15.775430	22.48847	NA	NA	NA	NA	NA	NA	4.556427	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	4.864913	9.248423	NA	NA	NA	NA	NA	NA	NA	3.893736	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	5.104697	16.115864	NA	NA	NA	NA	NA	NA	NA	5.177265	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	16.627023	27.186570	NA	NA	NA	NA	NA	NA	NA	11.044250	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	1815.233049	1140.509935	3149.77397	NA	NA	NA	361.9319	NA	37.06344	546.902894	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

[jhhughes256]

With the latest commit 472a0a2 the original issues with INCLUDEINTERPOLATION were fixed. However new regressions were introduced.

Include interpolation and extrapolation

New issues with 472a0a2.

• all profiles have missing values for AUC11_130, AUC60_124 & AUC60_100
• 39 profiles without AUC6_10 despite 10 not being an extrapolated time for these profiles (also occurs when interpolation is included but extrapolation is excluded).

knitr::kable(head(newData[,c(1, grep("^AUC\\d+_\\d+$", names(newData)), grep("^CONCTIME\\d+$", names(newData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	19.037484	62.309949	91.60590	98.11387	63.098301	NA	36.732628	NA	NA	13.778151	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	3.891138	15.775430	22.48847	24.74776	15.219666	NA	8.411666	NA	NA	4.556427	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	4.864913	9.248423	15.17517	15.17522	6.130309	NA	2.296925	NA	NA	3.893736	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	5.104697	16.115864	23.59851	23.82780	12.812288	NA	6.291580	NA	NA	5.177265	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	16.627023	27.186570	47.51955	47.69749	19.245042	NA	7.445251	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	1815.233049	1140.509935	3149.77397	3189.45272	832.210865	NA	361.931940	NA	NA	NA	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

Include extrapolation, exclude interpolation

Issues with commit cca452d fixed.

• 4 profiles without AUC0_64, 60_100 and 60_124 in the previous commit now have values.

knitr::kable(head(newData[,c(1, grep("^AUC\\d+_\\d+$", names(newData)), grep("^CONCTIME\\d+$", names(newData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	NA	62.309949	NA	98.11387	63.098301	NA	36.732628	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	NA	15.775430	NA	24.74776	15.219666	NA	8.411666	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	NA	9.248423	NA	15.17522	6.130309	NA	2.296925	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	NA	16.115864	NA	23.82780	12.812288	NA	6.291580	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	NA	27.186570	NA	47.69749	19.245042	NA	7.445251	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	NA	1140.509935	NA	3189.45272	832.210865	NA	361.931940	NA	NA	NA	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

Include interpolation, exclude extrapolation

Issues with commit cca452d fixed.

• 4 profiles without AUC0_64 in the previous commit now have values.

New issues with 472a0a2.

• All profiles without AUC60_100 despite 30 profiles having a final time of 120.
• 39 profiles without AUC6_10 despite 10 not being an extrapolated time for these profiles (also occurs when both interpolation and extrapolation are included).

knitr::kable(head(newData[,c(1, grep("^AUC\\d+_\\d+$", names(newData)), grep("^CONCTIME\\d+$", names(newData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	19.037484	62.309949	91.60590	NA	NA	NA	NA	NA	NA	13.778151	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	3.891138	15.775430	22.48847	NA	NA	NA	NA	NA	NA	4.556427	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	4.864913	9.248423	15.17517	NA	NA	NA	NA	NA	NA	3.893736	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	5.104697	16.115864	23.59851	NA	NA	NA	NA	NA	NA	5.177265	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	16.627023	27.186570	47.51955	NA	NA	NA	NA	NA	NA	NA	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	1815.233049	1140.509935	3149.77397	NA	NA	NA	361.9319	NA	NA	NA	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

[jhhughes256]

With the latest commit 19fc464 seems to have resolved all issues with INCLUDEINTERPOLATION with tc1590. I will double check these results against the HTML reports and confirm the behaviour extends to more complex tc1591. Provided these are correct this issue will close without further comment.

Include interpolation and extrapolation

Issues introduced in 472a0a2 resolved.

knitr::kable(head(newData[,c(1, grep("^AUC\\d+_\\d+$", names(newData)), grep("^CONCTIME\\d+$", names(newData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	19.037484	62.309949	91.60590	98.11387	63.098301	65.724934	36.732628	7.3711403	6.4956227	13.778151	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	3.891138	15.775430	22.48847	24.74776	15.219666	16.092465	8.411666	2.3810272	2.0219357	4.556427	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	4.864913	9.248423	15.17517	15.17522	6.130309	6.720872	2.296925	0.0009867	0.0040891	3.893736	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	5.104697	16.115864	23.59851	23.82780	12.812288	13.719644	6.291580	0.3297009	0.3686827	5.177265	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	16.627023	27.186570	47.51955	47.69749	19.245042	21.009201	7.445251	0.2364780	0.2474242	11.044250	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	1815.233049	1140.509935	3149.77397	3189.45272	832.210865	907.337515	361.931940	44.3411132	37.0634435	546.902894	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

Include interpolation, exclude extrapolation

Issues introduced in 472a0a2 resolved.

knitr::kable(head(newData[,c(1, grep("^AUC\\d+_\\d+$", names(newData)), grep("^CONCTIME\\d+$", names(newData)))]))

SDEID	AUC0_7	AUC8_48	AUC0_64	AUC0_168	AUC12_130	AUC11_130	AUC24_96	AUC60_124	AUC60_100	AUC6_10	CONCTIME1	CONCTIME2	CONCTIME3	CONCTIME4	CONCTIME5	CONCTIME6	CONCTIME7	CONCTIME8	CONCTIME9	CONCTIME10	CONCTIME11	CONCTIME12	CONCTIME13
2925168	19.037484	62.309949	91.60590	NA	NA	NA	NA	NA	NA	13.778151	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
40876220	3.891138	15.775430	22.48847	NA	NA	NA	NA	NA	NA	4.556427	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
63536292	4.864913	9.248423	15.17517	NA	NA	NA	NA	NA	NA	3.893736	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
111299859	5.104697	16.115864	23.59851	NA	NA	NA	NA	NA	NA	5.177265	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
112146587	16.627023	27.186570	47.51955	NA	NA	NA	NA	NA	NA	11.044250	0	0.5	1	1.5	2	2.5	4	8	12	16	24	48	72
123811839	1815.233049	1140.509935	3149.77397	NA	NA	NA	361.9319	NA	37.06344	546.902894	0	0.5	1	2.0	4	8.0	12	16	24	48	72	96	120

Include extrapolation, exclude interpolation

No new regressions.

Exclude extrapolation, exclude interpolation

No new regressions.